RESUMO
There are emerging concerns about the potential cerebral cortex injury from aspartame due to the accumulation of the various neurotoxic metabolic components in the central nervous system after long-term dietary exposure. The aim of this study was to evaluate the effect of oral aspartame consumption on cerebral cortex injury in the rat brain, and further evaluate the various underlying molecular mechanisms, with a special focus on oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis pathways. Sprague Dawley rats (nineteen, female) were randomly sub-divided into three groups: (i) normal diet with vehicle: control group (five rats), (ii) low dose of aspartame group (LA): seven rats received 30 mg/kg body weight (bw) daily doses of aspartame, (iii) high dose of aspartame group (HA): seven rats received 60 mg/kg bw daily doses of aspartame. After 8 weeks, the LA and HA groups showed lower expression levels of brain-derived neurotrophic factor (BDNF), antioxidant enzyme activity (SOD2, CAT), antioxidant marker (Nrf2), inflammatory response (IκB), mitochondrial biogenesis (Sirt1, PGC1α, Nrf1, TFAM), mitochondrial DNA (mtDNA) copy number, and apoptosis-related proteins (Bax, Caspase-3) expressions. Aspartame administration also elevated oxidative stress levels (Malondialdehyde, MDA), 8-hydroxy-2-deoxy guanosine (8-OHdG), PGE2 and COX-2 expressions, pro-inflammatory cytokines (TNFα, IL6, IL1ß), antioxidant marker expression (Keap1), inflammatory responses (iNOS, NFκB), and glial fibrillary acidic protein (GFAP) levels in the cerebral cortex of the rats, thereby contributing to the reduced survival of pyramidal cells and astrocyte glial cells of the cerebral cortex. Therefore, these findings imply that aspartame-induced neurotoxicity in rats' cerebral cortex could be regulated through four mechanisms: inflammation, enhanced oxidant stress, decreased mitochondrial biogenesis, and apoptosis pathways.
RESUMO
Frequent consumption of diet drinks was associated with oocyte dysmorphism, decreased embryo quality, and an adverse effect on pregnancy rate. We investigated the harmful effects of aspartame and potential mechanisms through which it increases infertility risk through clinical observations and in vivo and in vitro studies. Methods: We established a cohort of 840 pregnant women and retrospectively determined their time to conceive. We assessed the estrus cycle, the anti-Mullerian hormone level, ovarian oxidative stress, and ovarian mitochondrial function in an animal study. We also evaluated mitochondria function, mitochondrial biogenesis, and progesterone release with in vitro studies. Aspartame consumption was associated with increased infertility risk in the younger women (Odds ratio: 1.79, 95% confidence interval: 1.00, 3.22). The results of the in vivo study revealed that aspartame disrupted the estrus cycle and reduced the anti-Mullerian hormone level. Aspartame treatment also suppressed antioxidative activities and resulted in higher oxidative stress in the ovaries and granulosa cells. This phenomenon is caused by an aspartame-induced decline in mitochondrial function (maximal respiration, spare respiratory capacity, and ATP production capacity) and triggered mitochondrial biogenesis (assessed by examining the energy depletion signaling-related factors sirtuin-1, phosphorylated adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator-1α, and nuclear respiratory factor 1 expression levels). Aspartame may alter fertility by reserving fewer follicles in the ovary and disrupting steroidogenesis in granulosa cells. Hence, women preparing for pregnancy are suggested to reduce aspartame consumption and avoid oxidative stressors of the ovaries.